The long range objective of this grant proposal is the definition of the molecular structure-function relationships of the human factor VIII/von Willebrand (FVIII/vWF) protein(s). The following project are being emphasized: 1) experiments aimed at determining if the "dissociable" FVIII procoagulant activity protein is a proteolytic derivative of a single large parent molecule with a disulfide linked subunit structure that has both FVIII procoagulant and vWF activity; 2) efforts to define the structural features of the FVIII/vWF protein responsible for the FVIII procoagulant activity; and 3) the biochemical structural features of the FVIII procoagulant protein. Work aimed at further understanding the relationship of carbohydrate side chains to the expression of vWF activity will be continued by attempting to define more precisely the required carbohydrate structure. It is hoped that such biochemical studies will identify those structural features that are responsible for each of the two functional activities on this important molecule or complex.